Principles and Practice of Pharmaceutical Medicine

in Japan. However, the clinical development of

a foreign drug has to be duplicated in Japan

from phase I to phase III, because of potential

genetic differences, diet and medical practice

differences. Key data in the NDA are Japanese

data; the foreign clinical data package is only

considered as complementary information,

only used when safety issues are raised during

the approval process.

Some clinical pharmacology studies only can

be accepted as key data, such as drug interaction

studies or kinetic studies in renal or hepatic

insufficiency. The topic ‘Ethnic factors in foreign

data acceptability’ (E5) was passed in 1998 in

Japan and ended after six years of discussions; it

is now recognized that cultural factors are far

more important than genetic differences (ICH 2

Proceedings, 1993; ICH 3 Proceedings, 1995).

This allows for a regulated mutual recognition of

clinical data, which should significantly reduce

the number of useless duplications of clinical

studies and consequently save development

resources (see Chapter 18).

3. The import of a foreign study drug is strictly
   regulated: imported amount of bulk and/or
   pharmaceutical form should be clearly justified
   and limited to the exact quantity necessary for
   the development. When a clinical trial protocol
   is available, a copy has to be submitted for
   approval by a customs officer with a Drug
   Import Report Slip (Form 12) and a copy of
   the invoice. When the protocol is not available,
   a certificate from the Inspection and Guidance
   Division must be obtained after submission of
   the following documentation: an Import Report
   Form (Form 1), a Drug Import Report Slip
   (Form 13), a Memorandum (Form 2), a proto-
   col outline, a Memorandum stating that the
   protocol will be submitted within three months
   and a copy of the Drug Import business license.
   The labeling of the study drug should men-
   tion, on the drug packaging, container or wrap-
   per, the fact that the drug is for study purposes,
   the name and address of the institution, the
   chemical name or symbol, the manufacturing
   code number, storage instructions and expiry
   date.

The anticipated brand name, indications or

effects, and directions for use and doses of the

trial drug should not be mentioned on the drug

container or wrapper or on any document

attached to the trial drug.

35.5 New drug approval process

Content of the New Drug

Application (NDA)

Once the clinical development is completed, four to

sixmonths arenecessary topreparethepresentation

of the NDA, which should be as perfect as possible.

ThecontentoftheNDAisdefinedbythenotification

of April 1999, ‘Approval Application for Drugs’.

The ICH agreement induced several revisions in

July2001andJune2003,todescribethepreparation

of the CTD, enforced in April 2005.

Module I: Regulatory information such as applica-

tion forms and information on attached documen-

tation. Module 1 is region specific.

1. Table of content.


2. Approval application (copy).


3. Certificates.


4. Patent situation in Japan and abroad.


5. Background of origin, discovery and devel-
   opment.


6. Data related to conditions of use in foreign
   countries.


7. List of related products. Comparison of the
   main characteristics of the drug with those of
   similar drugs already registered in Japan.


8. Draft Package Insert.


9. International Non-proprietary Name (INN)
   and Japanese Accepted Name (JAN) publi-
   cations.

502 CH35 JAPANESE REGULATIONS